This chapter explores how mood problems relate to the endocrine changes of the natural menopausal transition (MT). It utilizes soundly conducted epidemiological studies to identify any relationship between depressed mood, menopausal status and hormone levels and to determine the relative importance in the aetiology of mid-aged women's depression of hormonal change, chronologic ageing, health problems and other stressors. Clinical conclusions regarding the relationship between menopause and mood are based on a small proportion of self-selecting women who may not be representative of most women's experience. More recent studies such as the USA based Study of 'Women's Health across the Nation' provide an indication of the role of ethnic factors in women's experience of the menopause. The perimenopausal patient requires a dual approach, with the clinician taking into account current research and treatment approaches to menopause and related symptoms, as well as the known research and treatment strategies for mood disorders.